Peripheral neural interfaces are intended to facilitate the exchange of information between the nervous system and electrical circuits that can be used to control sensorimotor prosthetic devices, to restore lost function due to nerve damage, and to improve human understanding of the fundamental mechanisms of nervous system operation. This exchange of information can be bidirectional, meaning that interfaces are capable of both recording and stimulating neural activity. While neural interface applications vary widely, it is generally desirable for the devices to provide a high degree of selectivity (i.e., to independently address large numbers of very small bundles of axons at geometries that approach the single micron scale) and to stay in place for long periods of time, up to many years if possible. Like other tissue interfaces and scaffolds, the physical properties of neural interfaces must be carefully tailored to provide the desired function while maintaining the health of the surrounding tissue system. Electrical properties must be tuned to enable the interface to reliably generate and/or sense the action potentials that travel in neurons. Recording electrodes are characterized primarily by their site impedance measured at the 1 kHz characteristic frequency, which ranges from approximately 50 kΩ to 1 MΩ. Neural stimulation requires safe reversible charge injection, typically at levels of tens of microamps for several milliseconds. Biphasic charge pulses are used to balance the total potential at the electrode-tissue interface, avoiding oxidation and protecting both the electrode and the surrounding tissue. Stimulating and recording microelectrodes typically range from tens of microns to several hundred microns in diameter, while extraneural macroelectrodes are generally larger. To maintain the quality of electrical connection required, neural interfaces intended for chronic use must also be highly biocompatible and must develop a healthy and intimate coupling to the nerve tissue. Therefore, surface biocompatibility, structural biocompatibility—including the minimization of forces applied to the nerve as it grows and moves—and conductivity of the nerve/device interface are required for a good neural interface.
One of the more promising neural interfaces that may enable a high degree of interconnectivity is the regenerative or sieve electrode type. Regenerative electrodes require the nerve to be transected and to re-grow through an artificial interface, ultimately reconnecting with the original or alternative tissue target. The regenerative electrode presents an opportunity to establish a permanent, integrated contact between the interface and the nerve. While highly invasive, this approach makes sense in cases where the nerve is already severed or in cases, such as amputation, where the efferent and afferent receptors that the nerve addresses are missing.
However, implementing a highly selective, healthy regenerative interface has presented a number of challenges. See A. Mannard et al., Science 183(4124), 547 (1974); D. J. Edell, IEEE Trans. Biomed. Eng. BME-33(2), 203 (1986); G. T. A. Kovacs et al., IEEE Trans. Biomed. Eng. 39(9), 893 (1992); T. Akin et al., IEEE Trans. Biomed. Eng. 41(4), 305 (1994); Q. Zhao et al., Biomaterials 18, 75 (1997); and A. F. Mensinger et al., J. Neurophys. 83, 611 (2000). In general, axons regenerate in greater numbers, to greater length, and with greater health through larger holes. See Q. Zhao et al., Biomaterials 18, 75 (1997); X. Navarro et al., Restorative Neurology and Neuroscience 9(3), 151 (1996); and S. P. Lacour et al., IEEE Trans. Neur. Sys. Rehab. Eng. 17(5), 454 (2009). However, larger holes decrease selectivity, creating a fundamental tradeoff between selectivity and quality of regeneration. Moreover, axons are sensitive to physical loading on the implant both during and after regrowth, and such loadings can cause high rates of axonal degeneration. See D. J. Edell, IEEE Trans. Biomed. Eng. BME-33(2), 203 (1986). A successful regenerative implant that could be seriously considered for chronic use in humans would need to withstand loading due to patient movement both during and after regeneration, and allow axons to grow without significant constriction.
Several approaches to interfacing between electronics and nerves have been evaluated previously and some have shown success including penetrating electrodes, sieve electrodes, and cuff electrodes. See A. Normann Richard, Nat. Clin. Pract. Neurol. 3(8), 444 (2007); W. L. C. Rutten, Annu. Rev. Biomed. Eng. 4, 407 (2002); K. H. Polasek et al., J. Neural Eng. 6(6), 066005 (2009). The elastic moduli of these state-of-the-art interface materials are orders of magnitudes higher than the modulus of the peripheral nerves which is around 0.45 MPa. See B. L. Rydevik et al., J. Orthop. Res. 8(5), 694-701 (1990). The compliance mismatch between the implant and the natural tissue creates stresses at the interfaces, impacting interface longevity and nerve health.
Common materials used for neural interfaces have included stainless steel, tungsten, platinum, platinum-iridium alloys, iridium oxide, titanium nitride, and PEDOT. See S. F. Cogan, Annu. Rev. Biomed. Eng. 10, 275 (2008). Most common materials that are highly electrically conductive, notably metals, are characterized by also having a large modulus of elasticity, low yield strain, and high surface hardness, meaning that they require large applied forces to deform significantly at either a surface or bulk level, and that even small deformations are permanent. Structures that include such materials (e.g. wires) can be made somewhat flexible by reducing physical dimensions. However, at the scale of peripheral nerves it becomes impractical to achieve additional flexibility by shrinking rigid conductive structures.
Therefore, a need remains for a regenerative neural interface and a method to fabricate the same that can provide significantly more mechanical flexibility at the interface to the nerve to accommodate both normal movement and natural axonal regrowth. In particular, a need remains for neural interfaces that are compatible with the mechanical properties of nerve tissue (i.e., generally have low elastic modulus, large yield strain, and low surface hardness) and simultaneously achieve high, selective and controllable electrical conductivity.